Zeolitic imidazolate frameworks activate endosomal Toll-like receptors and potentiate immunogenicity of SARS-CoV-2 spike protein trimer.

Nanomaterials offer unique opportunities to engineer immunomodulatory activity. In this work, we report the Toll-like receptor agonist activity of a nanoscale adjuvant zeolitic imidazolate framework-8 (ZIF-8). The accumulation of ZIF-8 in endosomes and the pH-responsive release of its subunits enable selective engagement with endosomal Toll-like receptors, minimizing the risk of off-target activation. The intrinsic adjuvant properties of ZIF-8, along with the efficient delivery and biomimetic presentation of a severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain trimer, primed rapid humoral and cell-mediated immunity in a dose-sparing manner. Our study offers insights for next-generation adjuvants that can potentially impact future vaccine development.

A microneedle vaccine printer for thermostable COVID-19 mRNA vaccines.

Decentralized manufacture of thermostable mRNA vaccines in a microneedle patch (MNP) format could enhance vaccine access in low-resource communities by eliminating the need for a cold chain and trained healthcare personnel. Here we describe an automated process for printing MNP Coronavirus Disease 2019 (COVID-19) mRNA vaccines in a standalone device. The vaccine ink is composed of lipid nanoparticles loaded with mRNA and a dissolvable polymer blend that was optimized for high bioactivity by screening formulations in vitro. We demonstrate that the resulting MNPs are shelf stable for at least 6 months at room temperature when assessed using a model mRNA construct. Vaccine loading efficiency and microneedle dissolution suggest that efficacious, microgram-scale doses of mRNA encapsulated in lipid nanoparticles could be delivered with a single patch. Immunizations in mice using manually produced MNPs with mRNA encoding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain stimulate long-term immune responses similar to those of intramuscular administration.

A quality assessment of YouTube content on shoulder instability.

OBJECTIVES: The Internet is a widely used resource for patients seeking health information, yet little editing or regulations are imposed on posted material. We sought to assess the quality and accuracy of information presented on shoulder instability on the online video platform YouTube. We hypothesize that YouTube videos concerning shoulder instability will be of little quality, accuracy, and reliability. METHODS: The first 50 YouTube videos resulting from the keyword query 'shoulder instability' were analyzed. The Journal of American Medical Association (JAMA) benchmark criteria (score range, 0-4) was used to assess video accuracy and reliability, and the Global Quality Score (GQS; score range, 0-5) was used to assess the quality of the video's educational content along with a generated Shoulder-Specific Score (SSS). RESULTS: The 50 videos observed collectively had 5,007,486 views, with the mean number of views being 100,149.72 ± 227,218.04. Of all videos observed, 32% were from a medical source and 56% had content relating to pathology information. The mean JAMA score was 2.84 ± 0.74, with the highest scores coming from academic sources. The mean GQS and SSS scores were 2.68 ± 0.84 and 5.30 ± 3.78. The mean GQS score was highest in videos from medical sources (3.3 ± 0.8) and videos about surgical technique/approach (3.2 ± 1.1). Advertisements were negative predictors of the JAMA score (ß = -0.324, P = 0.014), and academic (ß = 0.322, P = 0.015) and physician sources (ß = 0.356, P = 0.008) were positive predictors. CONCLUSION: YouTube videos on shoulder instability are of low quality and accuracy and are not reliable. Care providers should be aware of the overall low quality of information available on YouTube regarding shoulder instability.